Sleep and circadian disturbances in Alzheimer’s disease: clinical assessment, treatable syndromes, and limits of biomarker inference

Abstract

Sleep and circadian disturbances in Alzheimer’s disease (AD) affect patients and caregivers, but clinical action depends on the syndrome, measurement, and outcome under consideration. This narrative review links sleep assessment to indication-based care while distinguishing symptomatic benefit, physiological target engagement, and disease modification. A purposive literature search was supplemented by targeted checks of PubMed-indexed and original publisher records through 4 October 2026. Selected studies are described by population, AD ascertainment, comparator, and measured endpoint rather than assigned formal evidence-certainty grades. Actigraphy characterizes behavioral rest–activity patterns; melatonin timing and temperature rhythms address endogenous circadian physiology under controlled conditions. Polysomnography and quantitative electroencephalography characterize respiratory events, sleep architecture, and oscillatory activity. These measurements inform different questions and do not independently assign AD etiology or cognitive-functional stage. Clinical priorities include confirmed obstructive sleep apnea, cognition-adapted insomnia care, irregular sleep timing, medication-related effects, parasomnias, limb symptoms, and excessive daytime sleepiness. Interpretation incorporates hypoxemia, treatment exposure, comorbidity, caregiver support, and competing diagnoses. Randomized sleep benefits remain distinct from observational cognitive associations or exploratory imaging and cerebrospinal fluid changes. Human and animal studies of arousal circuits, protein dynamics, inflammation, and fluid transport provide mechanistic context, with conflicting results interpreted according to the actual experimental endpoint. The review provides a clinically organized account of selected evidence, not a comprehensive treatment ranking. Sleep care and cognitive-etiologic assessment should proceed in parallel, with follow-up matched to patient function, safety, and the specific treatment goal.